Neuroreport · 2026
Methyltransferase-like 14 alleviates neuronal ferroptosis in Alzheimer's disease by regulating the peroxiredoxin 6/apoptosis signal-regulating kinase 1 signaling pathway.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zheng Minghui, Hou Bingxu, Ma Ruxue, Tan Zheng
Аннотация
BACKGROUND: Alzheimer's disease is a neurodegenerative disorder, in which ferroptosis contributes to its pathogenesis and progression. This study explored the precise mechanisms of ferroptosis in the pathological development of Alzheimer's disease.
METHODS: Amyloid beta 1-42 oligomer-treated SH-SY5Y cells were used to simulate Alzheimer's disease in vitro. Ferroptosis was evaluated by detecting the levels of reactive oxygen species (ROS), malonaldehyde, glutathione, Fe2+, and ferroptosis-related proteins. Cell viability was assessed by a Cell Counting Kit-8 assay. Total RNA N6-methyladenosine (m6A) levels were detected using an RNA methylation quantification kit, and peroxiredoxin 6 (PRDX6) m6A levels were analyzed by m6A RNA immunoprecipitation. The binding of methyltransferase-like 14 (METTL14) to PRDX6 was investigated by a dual-luciferase reporter assay.
RESULTS: METTL14 levels were decreased in the serum of Alzheimer's disease patients and in an in-vitro model of Alzheimer's disease, and serum levels correlated with the degree of cognitive impairment. METTL14 overexpression significantly inhibited amyloid beta 1-42 oligomer-induced ferroptosis and cytotoxicity in SH-SY5Y cells. Mechanistically, METTL14-mediated m6A modification increased PRDX6 mRNA stability, which inactivated the ROS-apoptosis signal-regulating kinase 1/p38 pathway. Rescue experiments demonstrated that PRDX6 overexpression reversed sh-METTL14-induced ferroptosis and neurotoxicity.
CONCLUSION: METTL14 suppressed neuronal ferroptosis to delay Alzheimer's disease progression through m6A modification of PRDX6 to inactivate the ROS-apoptosis signal-regulating kinase 1/p38 pathway. Our observations provide a potential therapeutic strategy for Alzheimer's disease.
METHODS: Amyloid beta 1-42 oligomer-treated SH-SY5Y cells were used to simulate Alzheimer's disease in vitro. Ferroptosis was evaluated by detecting the levels of reactive oxygen species (ROS), malonaldehyde, glutathione, Fe2+, and ferroptosis-related proteins. Cell viability was assessed by a Cell Counting Kit-8 assay. Total RNA N6-methyladenosine (m6A) levels were detected using an RNA methylation quantification kit, and peroxiredoxin 6 (PRDX6) m6A levels were analyzed by m6A RNA immunoprecipitation. The binding of methyltransferase-like 14 (METTL14) to PRDX6 was investigated by a dual-luciferase reporter assay.
RESULTS: METTL14 levels were decreased in the serum of Alzheimer's disease patients and in an in-vitro model of Alzheimer's disease, and serum levels correlated with the degree of cognitive impairment. METTL14 overexpression significantly inhibited amyloid beta 1-42 oligomer-induced ferroptosis and cytotoxicity in SH-SY5Y cells. Mechanistically, METTL14-mediated m6A modification increased PRDX6 mRNA stability, which inactivated the ROS-apoptosis signal-regulating kinase 1/p38 pathway. Rescue experiments demonstrated that PRDX6 overexpression reversed sh-METTL14-induced ferroptosis and neurotoxicity.
CONCLUSION: METTL14 suppressed neuronal ferroptosis to delay Alzheimer's disease progression through m6A modification of PRDX6 to inactivate the ROS-apoptosis signal-regulating kinase 1/p38 pathway. Our observations provide a potential therapeutic strategy for Alzheimer's disease.